Over the past decade a burgeoning literature suggests that exercise has a therapeutic benefit in both patients with Parkinson's disease (PD) and in animal models of PD, especially when animals exercise at high intensity. Although many studies have been conducted and conventional wisdom acknowledges the beneficial effects of exercise, there have been no studies of: 1) the benefits of exercise in PD patients who have not yet started dopamine replacement therapy (patients with de novo PD), and 2) the dose-response effects of "moderate" versus "vigorous" exercise to attenuate the progression of PD symptoms in patients with de novo PD. Accordingly, the long-range goal is to determine whether exercise should be first-line therapy for de novo PD. As the first step in accomplishing our long-term goal, we will conduct a multi-center, randomized, controlled, single-blinded study of two intensities of endurance exercise over six months;we will also have a control "no- exercise" group. The two levels of exercise are moderate (4 days/wk at 60%-65% HRmax) and vigorous (4 days/wk at 80%-85% HRmax). We are proposing three aims. Aim 1 is to find out if patients can exercise at the higher level of intensity. Aim 2 is to find out if either or both of the exercie intensities yield benefits consistent with meaningful clinical change in the Unified Parkinson's Disease Rating Scale (UPDRS) (non-futility). Aim 3 is to document key responses associated with clinical trials, such as adverse events and attrition. Upon the completion of this study we will be well-positioned to conduct a phase III clinical trial if the futility trial is successful. e currently envision 6 possible successful scenarios based on the results of this exploratory study. These scenarios clearly indicate what parameters will be tested in the phase III clinical trial. Th scenarios are based not only on the outcome of the futility trial (Aim 2) but also on %HRmax attained and average number of days exercised (Aim 1). All 3 components are critical in planning the next study investigating exercise in PD. We also recognize the possibility the trial will be declared futile, which will force us to reconsider the therapeutic value of exercise for PD PUBLIC HEALTH RELEVANCE: Individuals with Parkinson's disease (PD) suffer from a slow and steady increase in symptoms of the disease and a progressive decline in function. Substantial evidence over the last decade suggests that endurance exercise can reduce the symptoms of the disease. This proposed phase II randomized clinical trial is designed to determine parameters of exercise intensity that attenuate progression of symptoms of PD. Upon the completion of this study, we will have defined the needed parameters for a phase III clinical trial.